PM_(2.5)/O_(3)暴露损伤细胞及线粒体的分子调控机制差异  

Differences in Molecular Regulatory Mechanisms of Cells and Mitochondria Damaged by PM_(2.5)/O_(3)Exposure

作　　者：吴婷婷 魏永杰[1,2] 李志刚 WU Tingting;WEI Yongjie;LI Zhigang(State Key Laboratory of Environmental Criteria and Risk Assessment,Chinese Research Academy of Environmental Sciences,Beijing 100012,China;College of Environmental Science and Engineering,Tongji University,Shanghai 200092,China)

机构地区：[1]中国环境科学研究院环境基准与风险评估国家重点实验室,北京100012 [2]同济大学环境科学与工程学院,上海200092

出　　处：《生态毒理学报》2025年第1期77-94,共18页Asian Journal of Ecotoxicology

基　　金：科技部重点研发计划项目(2022YFC3702603,2022YFC3703000)。

摘　　要：流行性病学研究表明,PM_(2.5)和O_(3)均与一些不良健康结局相关,如心肺、神经系统等相关疾病。在健康结局层面,PM_(2.5)和O_(3)的暴露效果具有一定的相似性。然而,PM_(2.5)/O_(3)的理化性质具有显著差异:PM_(2.5)是分散在大气中呈固态或液态的颗粒物;而O_(3)是具有强氧化性质的气体。生物体对不同性质的干扰有不同的防御及反应机制,故推测二者导致疾病发生的过程及分子调控机制可能存在差异。体外实验综述表明,氧化应激是PM_(2.5)及O_(3)造成损伤的重要机制。在细胞层面,PM_(2.5)主要通过诱导细胞内自噬相关的炎症反应发挥作用;而O_(3)通过攻击细胞膜上不饱和结构导致膜损伤。线粒体产能过程伴随着活性氧(ROS)的产生。当外界环境变化,细胞内的ROS平衡被打破,进而导致线粒体损伤。线粒体在细胞发育、代谢、信号传导及细胞命运调控等方面起着关键作用。近年来在线粒体层面的研究表明,PM_(2.5)暴露可引起细胞内离子变化,诱导与线粒体相关的生理变化;而O_(3)作为氧化分子直接损伤线粒体。本文综述了PM_(2.5)/O_(3)暴露导致的线粒体结构、功能、线粒体DNA(mtDNA)及相关信号通路的损伤机制,进一步探讨了二者在健康结局和疾病发生中的异同。通过阐明PM_(2.5)/O_(3)对线粒体及细胞损伤的机制,本文为大气污染相关疾病的预防和诊断提供了新的思路和研究方向。Epidemiological studies have shown that PM_(2.5)and O_(3)are associated with some adverse health outcomes,such as cardiopulmonary,neurological,and other system-related diseases.These adverse health outcomes induced by PM_(2.5)and O_(3)are similar.PM_(2.5)and O_(3)have distinct physical and chemical properties,with PM_(2.5)being a solid-liquid mixture and O_(3)being a strongly oxidizing gaseous pollutant.Biological organisms have distinct defense and response mechanisms for different environmental disturbances.Therefore,it is hypothesized that the processes and molecular regulatory mechanisms of diseases induced by PM_(2.5)and O_(3)exposure could be different.In vitro studies suggested that oxidative stress is an essential mechanism of damage caused by PM_(2.5)/O_(3).At the cellular level,PM_(2.5)primarily exerts its effects by inducing autophagy-related inflammatory responses,whereas O_(3)leads to membrane damage by attacking unsaturated structures in the cell membrane.The process of mitochondrial energy production is accompanied by the generation of reactive oxygen species(ROS).The imbalance of ROS oxidative and antioxidant reactions induced by PM_(2.5)and O_(3)exposure could lead to mitochondrial damage.Mitochondria play an essential role in cell development,metabolism,signal transduction,and regulation of cell fate.Recent studies indicated that PM_(2.5)exposure induced mitochondrial-related physiological alterations by modulating intracellular ion dynamics.In contrast,O_(3),as a potent oxidizing agent,directly inflicted damage on cellular structures,including mitochondria.This review provides a comprehensive summary of the damage to mitochondrial structure,function,mitochondrial DNA(mtDNA),and related signaling pathways caused by PM_(2.5)and O_(3)exposure.Furthermore,it explores the similarities and differences in health outcomes and disease processes between PM_(2.5)and O_(3).By elucidating the damage mechanism of PM_(2.5)and O_(3)to mitochondria and cells,this article offers new insights and research directi

关 键 词：PM_(2.5) O_(3) 线粒体 ROS MTDNA 疾病 

分 类 号：X171.5[环境科学与工程—环境科学]